Can endometriosis be hormonally reactivated in ovariectomized monkeys that have been spayed to suppress the disease? If so, such a system would permit precise sampling and evaluation of growth factors and other markers under experimentally controlled conditions. In our first trials of this approach, six rhesus monkeys were identified that had been diagnosed with endometriosis, surgically treated to remove a chocolate cyst (or lesion), and then ovariectomized 2+ years previously to control the disease. We treated these monkeys with estradiol (E2) and progesterone (P), to induce artificial menstrual cycles. During three artificial cycles, menstruation occured in all 6 monkeys following P withdrawal. The monkeys were laparotomized, and endometriotic tissue (if present) was harvested at the end of the 14 days E2, or at the end of 14 days of E2+P treatment. Reactivation was only successful in half the animals. At laparotomy, a large chocolate cyst was identified in 3 of the 6 monkeys. Samples of the cysts were fixed for histological study, frozen for immunocytochemistryof estrogen receptor (ER), P receptor (PR) and Ki-67 antigen, and frozen for RNA isolation. Analysis of the cysts revealed variable percentages of endometriotic glands and stroma, which expressed both ER and PR, but stromal cell steroid receptors had escaped from the type of regulation normally seen in endometrial tissues. All of the lesions expressed mRNA for keratinocyte growth factor but there was no difference in E2 treated vs P treated samples as there is in normal endometrium. We conclude that quiescent endometriosis in some rhesus monkeys can be reactivated by steroid hormones, and that abnormal patterns of steroid receptors and growth factors may exist. To make this model more efficient we plan to conduct the studies in a more prospective fashion by indentifying animals with disease, ovariectomizing them, and performing reactivation studies within a few months rather than a few years of ovariectomy, as it appears that the disease may completely disappear with time in some animals.